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      Combined Effects of Prenatal Exposures to Environmental Chemicals on Birth Weight

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          Abstract

          Prenatal chemical exposure has been frequently associated with reduced fetal growth by single pollutant regression models although inconsistent results have been obtained. Our study estimated the effects of exposure to single pollutants and mixtures on birth weight in 248 mother-child pairs. Arsenic, copper, lead, manganese and thallium were measured in cord blood, cadmium in maternal blood, methylmercury in maternal hair, and five organochlorines, two perfluorinated compounds and diethylhexyl phthalate metabolites in cord plasma. Daily exposure to particulate matter was modeled and averaged over the duration of gestation. In single pollutant models, arsenic was significantly associated with reduced birth weight. The effect estimate increased when including cadmium, and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) co-exposure. Combining exposures by principal component analysis generated an exposure factor loaded by cadmium and arsenic that was associated with reduced birth weight. MECPP induced gender specific effects. In girls, the effect estimate was doubled with co-exposure of thallium, PFOS, lead, cadmium, manganese, and mercury, while in boys, the mixture of MECPP with cadmium showed the strongest association with birth weight. In conclusion, birth weight was consistently inversely associated with exposure to pollutant mixtures. Chemicals not showing significant associations at single pollutant level contributed to stronger effects when analyzed as mixtures.

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          In utero programming of chronic disease.

          1. Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. 2. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension. 3. This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.
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            Ambient air pollution, birth weight and preterm birth: a systematic review and meta-analysis.

            Low birth weight and preterm birth have a substantial public health impact. Studies examining their association with outdoor air pollution were identified using searches of bibliographic databases and reference lists of relevant papers. Pooled estimates of effect were calculated, heterogeneity was quantified, meta-regression was conducted and publication bias was examined. Sixty-two studies met the inclusion criteria. The majority of studies reported reduced birth weight and increased odds of low birth weight in relation to exposure to carbon monoxide (CO), nitrogen dioxide (NO(2)) and particulate matter less than 10 and 2.5 microns (PM(10) and PM(2.5)). Effect estimates based on entire pregnancy exposure were generally largest. Pooled estimates of decrease in birth weight ranged from 11.4 g (95% confidence interval -6.9-29.7) per 1 ppm CO to 28.1g (11.5-44.8) per 20 ppb NO(2), and pooled odds ratios for low birth weight ranged from 1.05 (0.99-1.12) per 10 μg/m(3) PM(2.5) to 1.10 (1.05-1.15) per 20 μg/m(3) PM(10) based on entire pregnancy exposure. Fewer effect estimates were available for preterm birth and results were mixed. Pooled odds ratios based on 3rd trimester exposures were generally most precise, ranging from 1.04 (1.02-1.06) per 1 ppm CO to 1.06 (1.03-1.11) per 20 μg/m(3) PM(10). Results were less consistent for ozone and sulfur dioxide for all outcomes. Heterogeneity between studies varied widely between pollutants and outcomes, and meta-regression suggested that heterogeneity could be partially explained by methodological differences between studies. While there is a large evidence base which is indicative of associations between CO, NO(2), PM and pregnancy outcome, variation in effects by exposure period and sources of heterogeneity between studies should be further explored. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.
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              Prenatal glucocorticoids and long-term programming.

              Epidemiological evidence suggests that low birth weight is associated with an increased risk of cardiovascular, metabolic and neuroendocrine disorders in adult life. Glucocorticoid administration during pregnancy reduces offspring birth weight and alters the maturation of the lung and other organs. We hypothesised that prenatal exposure to excess glucocorticoids or stress might represent a mechanism linking foetal growth with adult pathophysiology. In rats, birth weight is reduced following prenatal exposure to the synthetic steroid dexamethasone, which readily crosses the placenta, or to carbenoxolone, which inhibits 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the physiological feto-placental 'barrier' to maternal glucocorticoids. As adults, the offspring exhibit permanent hypertension, hyperglycaemic, increased hypothalamic-pituitary-adrenal (HPA) axis activity and behaviour reminiscent of anxiety. Physiological variations in placental 11beta-HSD2 activity correlate directly with foetal weight. In humans, 11beta-HSD2 gene mutations cause low birth weight. Moreover, low-birth-weight babies have higher plasma cortisol levels throughout adult life, indicating HPA axis programming. The molecular mechanisms may reflect permanent changes in the expression of specific transcription factors, key among which is the glucocorticoid receptor (GR) itself. The differential programming of the GR in different tissues reflects effects upon one or more of the multiple tissue-specific alternate first exons/promoters of the GR gene. Overall, the data suggest that both pharmacological and physiological exposure prenatally to excess glucocorticoids programmes cardiovascular, metabolic and neuroendocrine disorders in adult life.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                12 May 2016
                May 2016
                : 13
                : 5
                : 495
                Affiliations
                [1 ]Environmental Risk and Health, Flemish Institute for Technological Research (VITO), 2400 Mol, Belgium; elly.denhond@ 123456wiv-isp.be (E.D.H.); greet.schoeters@ 123456vito.be (G.S.)
                [2 ]Department of Epidemiology and Social Medicine, University of Antwerp, 2610 Wilrijk, Belgium; sylvie.remy@ 123456uantwerpen.be
                [3 ]Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, 3590 Diepenbeek, Belgium; liesbeth.bruckers@ 123456uhasselt.be
                [4 ]Department of Public Health, Ghent University, Ghent, Belgium; FWO Research Foundation, 1000 Brussels, Belgium; isabelle.sioen@ 123456UGent.be
                [5 ]Department of Health, Provincial Institute for Hygiene, 2000 Antwerp, Belgium; Vera.NELEN@ 123456provincieantwerpen.be
                [6 ]Department of Analytical, Environmental and Geochemistry (AEGC), Vrije Universiteit Brussel, 1040 Brussels, Belgium; wbaeyens@ 123456vub.ac.be (W.B.); nicolas.vanlarebeke@ 123456ugent.be (N.V.L.)
                [7 ]Centre for Environmental Sciences, Hasselt University, 3590 Diepenbeek, Belgium; tim.nawrot@ 123456uhasselt.be
                [8 ]Department of Public Health & Primary Care, Leuven University, 3000 Leuven, Belgium
                [9 ]Department Sociology, Faculty of Political and Social Sciences, University of Antwerp, 2000 Antwerp, Belgium; ilse.loots@ 123456uantwerpen.be
                [10 ]Department of Biomedical Sciences, University of Antwerp, 2610 Wilrijk, Belgium
                [11 ]Department of Environmental Medicine, University of Southern Denmark, 5230 Odense, Denmark
                Author notes
                [* ]Correspondence: eva.govarts@ 123456vito.be ; Tel.: +32-1433-5166
                [†]

                These authors contributed equally to this work.

                Article
                ijerph-13-00495
                10.3390/ijerph13050495
                4881120
                27187434
                a833848c-f890-433a-a975-3a988dfae3eb
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 September 2015
                : 04 May 2016
                Categories
                Article

                Public health
                endocrine disruptors,mixtures,principal component analysis,regression analysis,birth outcome,epidemiology,biomonitoring,cord blood

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